Multi-target CAR T therapy for acute myeloid leukemia

Multi-center Phase I/II Clinical Trial of Multi-CAR T Cell Therapy for Acute Myeloid Leukemia

This study will try a CAR T-cell treatment that targets several AML surface markers in people with relapsed or refractory acute myeloid leukemia.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 2 Years to 75 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (Academic / other)
• Drugs / interventions: CAR T
• Locations: 3 sites (Guangzhou, Guangdong and 2 other locations)
• Trial ID: NCT03222674 on ClinicalTrials.gov

What this trial studies

This is a phase 1/2 program that engineers a patient’s own T cells with lentiviral vectors to express multiple chimeric antigen receptors recognizing AML surface proteins such as CD33, CD38, CD123, CD56, Muc1 and CLL1. After manufacturing, the multi-CAR T cells are infused back into patients to test feasibility, safety, and signals of anti-leukemia activity, with follow-up to measure persistence of the engineered cells. Eligible participants are people older than 2 years with relapsed or refractory AML whose malignant cells express one or more target antigens and who meet baseline organ-function and performance requirements. The protocol includes laboratory monitoring for toxicity, response assessments, and correlative studies to track CAR T-cell function over time.

Who should consider this trial

Good fit: Ideal candidates are people over 2 years old with relapsed or refractory AML whose leukemia cells express one or more of the listed antigens and who have adequate organ function, good performance status, and no uncontrolled infections.

Not a fit: People whose leukemia does not express the target antigens, who have uncontrolled infections, poor organ function, or very limited life expectancy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the therapy could produce remissions in some people with relapsed or refractory AML by targeting multiple leukemia antigens and reducing antigen-loss escape.

How similar studies have performed: Early-phase CAR T approaches in AML have produced occasional responses but overall limited durability, and multi-target CAR strategies are relatively new with only preliminary clinical data to date.

Eligibility criteria

Inclusion Criteria:

1. Age older than 2 years.
2. CD33, CD38, CD56, CD123, MucI, and CLL1 expression can be identified in the malignant cells by immuno-histochemical staining or flow cytometry.
3. Karnofsky performance status (KPS) score is higher than 80 and life expectancy \> 2 months.
4. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤ 2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL.
5. Hgb≥80g/L.
6. No cell separation contraindications.
7. Abilities to understand and the willingness to provide written informed consent.

Exclusion Criteria:

1. Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
2. Active bacterial, fungal or viral infection not controlled by adequate treatment.
3. Known HIV or hepatitis B virus (HBV) infection.
4. Pregnant or nursing women may not participate.
5. History of glucocorticoid for systemic therapy within the week prior to entering the test.
6. Previously treatment with any gene therapy products.
7. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Where this trial is running

Guangzhou, Guangdong and 2 other locations

• Zhujiang Hospital of Southern Medical University — Guangzhou, Guangdong, China (Recruiting)
• Shenzhen Geno-immune Medical Institute — Shenzhen, Guangdong, China (Recruiting)
• Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center — Kunming, Yunnan, China (Recruiting)

Study contacts

• Principal investigator: Lung-Ji Chang — Shenzhen Geno-Immune Medical Institute
• Study coordinator: Lung-Ji Chang

Conditions Acute Myeloid Leukemia; AML; CAR T; Muc1,CLL1, CD33, CD38, CD56, and/or CD123